Merck Uses Legal Threats To Stifle Negative Advice About Zetia And Vytorin

Merck Uses Legal Threats To Stifle Negative Advice About Zetia And Vytorin In Italy

   

 

In response to repeated legal threats, a public health doctor in Italy has withdrawn advice to curtail use of a controversial drug. The drug, ezetimibe, is a key ingredient in Zetia and Vytorin, which is manufactured by Merck Merck. The cholesterol-lowering drug has been the subject of fierce controversy because it has never been shown to improve clinical outcomes. Despite the controversy, in 2013 the drugs had combined sales of more than $2.6 billion.
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Should Everyone Be Taking Cholesterol-Lowering Drugs? - Eenfeldt

Should Everyone Be Taking Cholesterol-Lowering Drugs?

Andreas Eenfeldt, MD.

 

Should everyone over 50 be treated with cholesterol-lowering drugs, regardless of whether they suffer from heart disease?

 

A new review of previous research shows that even people with no history of heart disease may slightly lower their risk for heart disease with preventative statin medication*.

Independent.co.uk: ‘Millions’ more to be prescribed statins to beat high cholesterol
There are three reasons to be skeptical of mass medication of the healthy population:

1

All studies included in the review were sponsored by pharmaceutical companies, that sell the drugs involved. It’s not controversial that this leads to positive effects being exaggerated and negative side effects being silenced.

When big money like this is at stake, pharmaceutical companies will use every trick in the book. One of the more obvious examples was when the gigantic JUPITER trial was prematurely terminated by AstraZeneca, just when the figures for their drug happened to look good.

2

These are not harmless vitamin pills we’re talking about. Statins come with relatively frequent side effects, such as muscle pain, muscle weakness, fatigue, a slightly reduced cognitive functioning (on average) and an increased risk of diabetes.

3

The reduction in risk of heart disease in previously heart healthy individuals is hardly great. According to this review the chance of preventing a heart attack, or a similar event, by taking a drug for five years is 1.8 percent! Thus, there is a 98.2 percent likelihood that taking the drug for five years doesn’t protect against such health problems. The risk of troublesome side effects? Significantly greater than the chance of any benefit.

Note that a 1.8 precent chance of benefitting from five years of medication only applies if we blindly trust the pharmaceutical companies’ own studies. Most likely the results are exaggerated, so the chance of a benefit would likely be significantly less than 1.8 percent.

1+2+3+=

Most people probably wouldn’t accept the risk of side effects and long-term medication if told about the 98 percent (at least) risk of having done so in vain.

Would you?
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Beware: new cholesterol lowering drugs coming - Kendrick

Beware: new cholesterol lowering drugs coming

by Dr Malcolm Kendrick

‘…across the gulf of space, minds that are to our minds as ours are to those of the beasts that perish, intellects vast and cool and unsympathetic, regarded this earth with envious eyes, and slowly and surely drew their plans against us.’ War of the Worlds

An era is coming to an end. Statins, the world’s most widely prescribed and profitable drugs, have, with the exception of Crestor (rosuvastatin), all come off patent and their price has plummeted. Good news for NHS accountants: not so good for company profits.

So a supposedly new, improved, much safer and more effective generation of cholesterol lowering drugs will soon be available at a doctor’s surgery near you. At least that will be the general tone of the marketing. With 80% of the population suffering from “high” cholesterol, according to guidelines drawn up by consultants with links to drug companies, there is obviously a huge need. (For an account of how seriously we should take this “need” see Dr John Briffa’s post.)

This is obviously a great opportunity for the companies but it also faces them with a fascinating dilemma. Statins have been relentlessly promoted as the most beneficial l class of drugs ever, protecting not just against cardiovascular disease but also Alzheimer’s and Parkinson’s and being virtually side-effect free into the bargain.

An alarming press release

But if the companies are going to persuade those NHS accountants and cash-strapped GP commissioning bodies to start paying serious prices for the new drugs, they need to persuade them that statins actually had a serious problem all along but it is one that can be avoided by buying the new products.

Recently I received a press release by email that was the first sign that this process is already underway. It was a warning about something called P9 which, had I been a loyal statin believer, I would have found pretty alarming. After explaining how statins worked by targeting an enzyme known as HMG-CoA in the liver, the email went on to tell me this:

“However, statin treatments have been shown to actually stimulate the production of PCSK9, which is counterproductive, possibly damaging to the liver, and ultimately limits the treatment’s ability to lower LDL cholesterol levels.”

Why weren’t we told about this risk before?

What on earth is PCSK9, you and the medical statin believers might well ask. And if it is not only able to damage the liver but also render the whole purpose of taking a statin self-defeating, why haven’t we been told about it before?

Here was a classic marketing ploy; tell you about a problem and immediately offer a solution in the form of a drug that is able to block the production of damaging PCSK9. The full name of these new drugs is proprotein convertase subtilisin/kexin type 9 inhibitors.

And it’s not the only dauntingly high tech-new cholesterol lowering drug that could be coming your way in the not too distant future. For the sake of completeness here is a list of nearly all the new compounds waiting in the wings. Some will undoubtedly founder on the rocks of side effects that are just too dangerous, never to be seen again.

Other new drugs in the race

• Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors)
• Antisense oligonucleotides (ASOs) targeting the production of apolipoprotein B-100 (apoB-100)
• Microsomal triglyceride transfer protein inhibitors
• Squalene synthase inhibitors
• Peroxisome proliferator-activated receptor agonists
• Thyroid hormone receptor agonists

For the moment though my money for the first out of the gate are the PCSK9 inhibitors, which I will call P9 inhibitors. So what exactly are they? Well P9 is an enzyme that is found mainly in the liver. It binds to receptors that remove the “bad” LDL (low density lipoprotein) cholesterol and destroys them after they have taken just one LDL molecule out of circulation, meaning that they can’t be reused to remove more LDL.

But if you block P9, you allow LDL receptors to continue removing LDL merrily from the bloodstream, so LDL levels fall dramatically. In fact P9 inhibitors appear to lower LDL far more effectively than statins which, if you sign up to the belief that the lower your cholesterol goes the more protection you get, this can only be another major benefit.

The new statin combo

What’s clever about this is that it avoids taking on statins directly. Given how familiar doctors are with them, how most believe in them and how cheap they are, a head on attack would be doomed to failure.  The manufacturers know, damn well, that doctors are not just going to stop using statins, so their P9 inhibitors will be positioned to sit alongside statins, allowing them to work, supposedly, even more safely.  At first anyway.

But there is more to this press release and I could pick it apart for hours, marvelling at the ability to say so much – in so few words. But let’s just focus on the phrase…’possibly damaging to the liver’ in relation to statins. Now, I know that statins do damage the liver – to a greater or lesser degree. Liver enzymes in the blood (a sign of liver damage) are often raised to three times normal levels – sometimes more.

But why not focus on the side-effect that is most clearly recognised with statins?  Namely muscle damage and pain. This is the true Achilles heel of statins. Yet the press release talks about liver damage…

Danger to your liver

The most likely reason is that P9 inhibitors have been found to cause liver problems themselves in both animal studies and phase 1 studies on human volunteers. Knowing their mechanism of action, it is more than likely that PCSK9 blocking agents could damage the liver. If you over-ride negative feedback mechanisms, the body doesn’t like it very much, as you will be overloading cells with toxic waste products. Enzymes to break down LDL receptors are there for a reason.

So, we can expect P9 inhibitors are going to cause liver damage. However, by attacking statins for causing liver damage, the pharmaceutical companies will be hoping to mask the most serious adverse effect of the new drug. The words used to defuse concerns about this problem will be something along the lines of. ‘With our P9 inhibitor we have seen mild elevations of liver enzymes in clinical studies. However, they are similar to those caused by statins, are reversible and cause no long-term damage.’ Blah, blah….  ‘Move along, nothing to see here.’

This fear is not just based on a vague unease that if you block a feedback mechanism in the body you are probably heading for disaster. It is also based on the fact that, if the companies developing P9 inhibitors are already blaming statins for causing liver damage, they are doing to hide their own problems behind a smokescreen. You heard it here first.

I also predict that severe liver damage problems will take years to emerge. In most people the liver is pretty resilient – it takes a lot of alcohol and a lot of time to destroy it. I fear that clinical studies will not be long enough to demonstrate this effect –before the drugs are launched and widely prescribed. I can say all this because it is what has happened with damaging block buster drugs in the past, such as the anti-inflammatory Vioxx and and the diabetes drugs Avandia.

My predictions for P9 inhibitors:

• They will be widely promoted as the new statins
• Pfizer, or Merck, will buy out the patent to one of the new products (they may have already done this)
• They will be launched without any long-term studies to show they actually cut your chance of dying from a heart attack. They will be approved purely on the basis that they lower cholesterol/LDL cholesterol.
• They will make billions upon billions in the first two years and be hailed around the word as a new generation in cholesterol lowering. The chief executives of the companies selling these drugs will be paid massive bonuses
• Key Opinion Leaders (‘experts’) will promote them ruthlessly at major conferences and press launches
• Reports of a high level of liver damage/deaths will  start to emerge
• The companies will deny there is a problem and attack anyone who says there is one
• They will start to be withdrawn from the market two to three years after launch
• There will be lawsuits
• The companies will be fined a small fraction of the profits they made from hyping the drugs
• It will emerge that the problems with liver damage were known by the companies many years before the drugs were launched but not many people will be interested by then, as the next generation of lipid lowering agents will be arriving
• No-one will be held accountable

Yes, the great Nostrokendrickos has spoken.
In the meantime remember that ‘Something unpleasant this way comes’.
Disclosure: I do not believe that a raised LDL/cholesterol level causes heart disease.
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So much for scientific debate - Kendrick

   So much for scientific debate

I thank Ted Hutchinson for pointing me at this article in the Irish Independent. It appeared on the 5^th of October, and I reprint it in full, here.

A LEADING vascular surgeon, whose research review concluded cholesterol-lowering medicines may do more harm than good for many otherwise healthy people, has been gagged by the Health Service Executive.

 

Sherif Sultan, a senior medic at University College Hospital, Galway, reviewed a range of studies of statins and found a lack of evidence to show they should be given as a means of prevention to healthy people with high cholesterol but no heart disease.

Mr Sultan and his surgeon colleague Niamh Hynes said lifestyle changes to reduce cholesterol were better because this allowed people to avoid the risk of statins’ side effects.

 

However, in a statement last night, Dr Pat Nash, a cardiologist and the group clinical director in University College Hospital said the recently published views of his colleagues were “not representative” of those in Galway or neighbouring hospitals.

 

“As group clinical director of the West/North West Hospitals Group, and a working cardiologist, I wish to reassure patients that statins are safe,” said Dr Nash.

 

“These are very important, well-validated drugs for the treatment of elevated cholesterol. We have extensive evidence to show their benefit and to show that they improve outcomes for patients with heart disease and stroke and that they have a role in preventing heart disease and stroke.

 

“As always, if patients have any concerns, they should not discontinue their medication without discussing with their GP or consultant.”      

 

Asked to comment, Mr Sultan said: “I have received an official warning from the HSE and have been instructed not to liaise directly with the press in my capacity as a HSE consultant.” However, he said he could continue to comment as a consultant vascular surgeon at the Galway Clinic, where he has a private practice.

 

The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant. He said he stood by his analysis of the role of statins in otherwise healthy patients with high cholesterol. He pointed to another recently published review on exercise versus drug therapy in the management of pre-diabetes and cardiovascular disease.

 

“That ‘British Medical Journal’ analysis showed the superiority of exercise over drug therapy extends even to secondary prevention (where patients have developed disease)¹.

 

This story has been rumbling on for a while. A report on the research paper can be found in the Irish Medical Times from a couple of weeks before.

The under-reporting of findings on major adverse effects of statin therapy and the way in which they had been withheld from the public, and even concealed, is a scientific farce, claims new Irish research.

 

Mr Sherif Sultan, Consultant Vascular and Endovascular Surgeon, and Niamh Hynes, Clinical Lecturer In Vascular and Endovascular Surgery, claimed their study, just published in the Journal of Endocrine and Metabolic Diseases (2013, 3, 179-185) highlights the major side-effects and dangers of statins.

 

They said there is a categorical lack of clinical evidence to support the use of statin therapy in primary prevention. They are both based in the Western Vascular Institute at University College Hospital Galway and the Galway Clinic. “Odds are greater than 100-to-1 that if you’re taking a statin, you don’t really need it²..

 

I was sent the original paper by Sherif Sultan a couple of months ago, and it is very scathing about statins….. very scathing indeed. It even suggests, perish the very thought, that pharmaceutical companies may have been trying to present statins in the best light possible. I find such a suggestion almost impossible to believe. Knowing how completely ethical these companies are.
Anyway, I suppose the key phrase in all of this sorry episode is the following:

“The HSE declined to comment on the reasons for ordering Mr Sultan not to speak as a public consultant.”
If the Health Service Executive were to comment, what could they say to justify their actions?
“The hell with scientific debate. He should just damned will shut up and say what we want him to say?”
“How dare anyone criticise the sainted statins which work in mysterious ways their wonders to perform.”
“We expect utter loyalty from those who work in the glorious Irish Health Service. Those who do not support us can expect serious sanctions……”

On balance, declining to comment is probably the best policy for the HSE. Because if you start trying to justify why you are gagging a researcher for trying to tell the truth then, well, you will end up having to justify state censorship of scientific debate. Which never looks that good on the printed page, I find.

I feel I should sign off this blog with a quote from George Orwell, taken from 1984. “Being in a minority, even in a minority of one, did not make you mad. There was truth and there was untruth, and if you clung to the truth even against the whole world, you were not mad.”

1: http://www.independent.ie/irish-news/hse-gags-surgeon-after-cholesterol-drug-claims-29636095.html
2: http://www.imt.ie/news/latest-news/2013/09/study-claims-to-highlight-the-ugly-side-of-statins.html
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Statins Do Not Save Lives - Smith

New Study Confirms Statins Do Not Save Lives

Thursday, August 29, 2013

 

A 'new' study of statin medications has just been published in the Journal of the American College of Cardiology. I say new, but actually its a new manipulation of old data.

The researchers looked at eight previously conducted clinical trials done on statins. The population studied was elderly people without existing cardiovascular disease. After doing their calculations, it was concluded that statins did slightly reduce the risk of heart attack and stroke, but the use of statins did not reduce the risk of death from cardiovascular disease. There was also no reduction in the risk of death from all causes.

The bottom line is that it has once again been established that statins do not extend life expectancy for people without cardiovascular disease.

This is one of the key points that STATIN NATION exposes.  The video excerpt below provides a summary of this issue:



A Bit More Detail
Around 75% of all the people who take a statin, are taking it for  primary prevention. This means they do not have a heart problem but are taking the medication in the hope of preventing a heart problem in the future.  When it comes to primary prevention none of the largest clinical trials have been able to conclusively show any net benefit.

The AFCAPS (1), ASCOT (2), CARDS (3), PROSPER (4) and WOSCOPS (5) clinical trials all failed to show a statistically significant reduction in all cause mortality (deaths from all causes, not just heart disease related deaths).

All cause mortality data, of course, is the only true measure one can use to determine if a statin is going to extend life expectancy or not. Whilst some clinical trials of statins have shown a very slight reduction in heart disease, in primary prevention, this has always been countered by deaths from other causes. The net result is that people do not live any longer after taking a statin.

In 2010, a meta-analysis of 11statin trials was published in the Archives of Internal Medicine. Professor Kausik Ray and colleagues concluded that statins provided no benefit in terms of deaths from all causes, when used for primary prevention (6). This analysis had the “cleanest” dataset of any analysis completed to date - the researchers were able to exclude patients with existing heart disease (known as secondary prevention) and only include data associated with primary prevention.
When we look at the use of statins for people who already have a diagnosed heart problem (the 25% of people, in secondary prevention) the picture becomes less clear cut. Some trials have found significant increases in life expectancy for these people, however, the trials have always been too short for us to assess the long-term impact of being on a statin.

Even if statins do provide a short-term benefit for those with a heart problem, it is debatable that this has anything to do with the cholesterol-lowering effect of statins. Quite simply, the amount of benefit does not match up with the degree of cholesterol-lowering. The potential beneficial affects of statins for people with heart disease is now widely recognised to be associated with a reduction in inflammation. And recent evidence suggests that this is mediated through an improvement in iron metabolism (7).

“Benefits Outweigh Risks” 
Any decision to take a medication should of course involve a clear understanding of the benefits balanced against the risks. Many authorities have repeatedly stated that the benefits of statins far outweigh the risks. Clearly, this is not correct.

First of all, as we have seen above, there is no net benefit for the 75% of people who take a statin in primary prevention. So, for these people, the choice should be abundantly clear, since they will only expose themselves to the significant adverse effects associated with statins.

Statins have been linked with more than 300 different adverse effects. The most common adverse effects include: depression, suicide, sleep disturbances, memory loss, sexual dysfunction, lung disease, muscle-related problems, cognitive loss, neuropathy, pancreatic dysfunction and liver dysfunction. More recent studies have also shown that statins cause type 2 diabetes and acute kidney injury.

In addition, many doctors are concerned about statins and a potential increase in the risk for cancer and heart failure. A recent study found that the long term use of statins doubles the risk of breast cancer in women.

The best estimates suggest that at around 20% of the people who take a statin will experience significant adverse effects. This needs to be considered when thinking about both primary and secondary prevention, since this 20% is a much greater number than the number of people who might benefit, even in secondary prevention.

References: 
1. Downs JR, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998; 279:1615-22.
2. Sever PS, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361:1149-1158.
3. Clhoun HM, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atovastatin Diabetes Study (CARDS). Lancet 2004; 364:685-696.
4. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002; 360:1623-1630.
5. Shepherd J, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia (WOSCOPS). N Engl J Med 1995; 333:1301-1307.
6. Ray KK, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med. 2010; 170:1024-31.
7. Zacharski, LR et al. The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention. American Journal of Public Health. Published online ahead of print February 14, 2013.
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Should Women take Statin Drugs – ever? - Watson

http://dietheartnews.com/2012/11/should-women-ever-take-statin-drugs/

Should Women take Statin Drugs – ever?

Alan Watson | November 27, 2012 |

 

A true story…

In 1987, Mevacor, the first statin cholesterol-lowering drug, was introduced in record short time. Within a decade, Zocor, Pravachol, Lescol, Lipitor and Baycol were added. In August 2001, after 31 deaths from a muscle-destroying side effect, Bayer of Germany withdrew Baycol.

While clinical studies have demonstrated a small benefit among people with active, late stage heart disease, the threat of muscle-destroying side effects, liver damage and cancer are on the rise.

As reported in the Felix Letter, in the “supposedly successful” Simvastatin trial (Zocor), where the average life extension in the treatment group after 5 years was 24 days, Dr. Louis Krut is quoted as saying:

“If we were to set a very modest goal to extend their average life by only 1 year, it would require them to take simvastatin for 83 years.”

 

According to Dr. Uffe Ravnskov, statin drugs may stimulate cancer. Because the latency period between exposure and incidence is as long as 20 years, we do not know the extent to which the statin drugs will increase the rate of cancer in coming decades.

In the CARE study (Pravachol), 12 women in the treatment group developed breast cancer compared to just one in the control group (not taking the drug). And blood levels in the patients taking statin drugs were close to those that cause cancer in rodents.

Why take a chance with muscle-destroying side effects, liver failure and cancer? That’s what I asked my now deceased mother-in-law several years ago when she started taking Zocor.

Doris’s total cholesterol was 285. She was a little overweight but, at age 72, she was enjoying life and had no history of chronic illness. She drove a car, went shopping, and was even looking for a boyfriend!

As she lay in ICU one year later with elevated liver enzymes and a serious blood infection, her doctor took her off of Zocor. Once she stabilized, suspecting the drug had caused harm, we asked her doctor to recheck her cholesterol.

Yes – Doris was dying, but why not see if the drug treatment nonetheless had succeeded in lowering her cholesterol. When the doctor reluctantly complied – it took a letter from the family – Doris’s cholesterol was 130 – a drop of 155 mg/dl in less than a year.

After a few more agonizing hospitalizations, Doris was dead – Zocored within a year of starting the drug. Her doctor said she died of leukemia. Women – don’t let this happen to you. There are no circumstances – ever – when a woman should take a drug to lower cholesterol.

Women with higher cholesterol – live longer. Also, you must ask your doctor for a complete lipid evaluation. Just focusing on total cholesterol is a serious medical mistake. The ultimate price you may pay is an agonizingly slow death from cancer, liver failure or leukemia.
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How doctors actually get paid more for writing more statin prescriptions - Shanahan

How doctors actually get paid more for writing more statin prescriptions Statin Payments

Catherine Shanahan


You may have read that doctors receive payment or bonuses for prescribing statins, the cholesterol-lowering drugs. I'm a chapter leader in Kauai, and a family physician, so I'm in a good position to fill in some details about how doctors actually get paid more for writing more statin prescriptions. The mechanism is a little cumbersome to describe clearly, but I'll take a stab at it.We have a series of "quality measures" that are tracked by the insurance company. One quality measure is the number of mammograms we do on our patients between ages 40 and 69, another is that we send our diabetic patients to the eye doctor once a year for retinal exams. For our patients who carry a diagnosis of "coronary artery disease," we have to write them a prescription for a cholesterol-lowering drug. If any one doctor doesn't follow any one of these imperatives, he loses points toward a cash bonus, and the entire group is similarly penalized. As you can imagine, there is lots of peer pressure to prescribe!

Actually, we don't get our bonus unless the patient goes and buys the drug or gets the test or sees the eye doctor and so on, so it's not enough just to write the prescription, we have to talk up the drug enough to get them to go out and buy it. Currently, there are only a few means by which a person can be labeled as a patient with coronary artery disease. Having a heart attack is one, and having abnormal results on heart tests (like angiograms) is another. Diabetes is now considered a "coronary artery disease equivalent" and so, in the near future, doctors may be required to get all our patients who have type one or type two diabetes to take their statins, or lose more money.

These HMOs are insurance companies like Blue Cross, which offer their clients (employers and patients) HMO programs. The HMO plan we have is offered by HMSA (Hawaii Medical Something Something). For whatever reason, HMSA wants to offer an HMO program for people, and doctors who participate as providers must comply with the rules of the program and accept payments according to the rules. There are clear benefits to pharmaceutical companies in this structure but no obvious reason why HMSA would want to encourage people to buy expensive drugs that HMSA must pay for. One might speculate that there are some quid-pro-quo relationships between the insurance companies and the pharmaceutical companies, but I have no idea what they are. However the ties are structured, I feel, as do many other scientists, that these kinds of business relationships lead to behaviors that pose real threats to patient care, and to human health in general. Because industrial connections like this fund most research, they distort the scientific process and are far more insidious, invisible, and totalitarianistic than expensive dinners and trips to Hawaii, which are what the media would have us believe is the sum total of the problem.

By the way, the bonus is actually not a bonus at all. This is where it gets Orwellian. We give up a certain percentage of the payment for accepting HMO patients, and we get it all back, in theory, if we meet all of our quality measures. We never do because of computer glitches which continually fail to track our prescribing, testing, and referring patterns accurately. Nobody can explain why we've agreed to accept HMO insurance plans, but we seem to feel we have no choice. And we will have less choice before long; Medicare is planning to begin similar programs. Each of these programs takes more money away from the doctors and gives it to middle managers, ensures that drug companies get more money, and that expensive tests of limited value are done more often.

These are some reasons why savvy business people are going into "alternative" medicine where they benefit from cash payments and total autonomy. Several here on Kauai are making millions.

Catherine Shanahan MD

Kalaheo, Hawaii

This article can be accessed at: http://www.westonaprice.org/letters/754-letters-winter-2006?qh=YTozOntpOjA7czo5OiJjYXRoZXJpbmUiO2k6MTtzOjg6InNoYW5haGFuIjtpOjI7czoxODoiY2F0aGVyaW5lIHNoYW5haGFuIjt9

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Important safety label changes to cholesterol-lowering statin drugs

FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs

Facts about statins

A class of prescription drugs used together with diet and exercise to reduce blood levels of low-density lipoprotein (LDL) cholesterol (“bad cholesterol”) Marketed as single-ingredient products, including Lipitor (atorvastatin), Lescol (fluvastatin), Mevacor (lovastatin), Altoprev (lovastatin extended-release), Livalo (pitavastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Zocor (simvastatin) Also marketed as combination products, including Advicor (lovastatin/niacin extended-release), Simcor (simvastatin/niacin extended-release), and Vytorin (simvastatin/ezetimibe)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Safety Announcement

[2-28-2012] The U.S. Food and Drug Administration (FDA) has approved important safety label changes for the class of cholesterol-lowering drugs known as statins. These changes were made to provide the public with more information for the safe and effective use of statins and are based on FDA’s comprehensive review of the statin class of drugs (see Data Summary below). The changes include the following:

Infographic About Cholesterol and Statins1 2

Monitoring Liver Enzymes
Labels have been revised to remove the need for routine periodic monitoring of liver enzymes in patients taking statins. The labels now recommend that liver enzyme tests should be performed before starting statin therapy and as clinically indicated thereafter. FDA has concluded that serious liver injury with statins is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury.

Adverse Event Information
Information about the potential for generally non-serious and reversible cognitive side effects (memory loss, confusion, etc.) and reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels has been added to the statin labels. FDA continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.

Drug Interactions
The lovastatin label has been extensively updated with new contraindications (situations when the drug should not be used) and dose limitations when it is taken with certain medicines that can increase the risk for muscle injury (see Lovastatin Dose Limitations below).

Healthcare professionals should refer to the drug labels for the latest recommendations for prescribing statins (also see Additional Information for Healthcare Professionals below). Patients should contact their healthcare professional if they have any questions or concerns about statins.

Additional Information for Patients

• The statin drug labels have been revised to provide patients with more information on the safe and effective use of statins. Patients should be aware of the following information:
  • There have been rare reports of serious liver problems in patients taking statins. Patients should notify their healthcare professional right away if they have the following symptoms: unusual fatigue or weakness; loss of appetite; upper belly pain; dark-colored urine; or yellowing of the skin or the whites of the eyes.
  • Memory loss and confusion have been reported with statin use. These reported events were generally not serious and went away once the drug was no longer being taken.
  • Increases in blood sugar levels have been reported with statin use.
  • Certain medicines should never be taken (are contraindicated) with lovastatin (Mevacor) (see Lovastatin Dose Limitations below).
• Patients should contact their healthcare professional if they have any questions or concerns about statins.
• Patients should report side effects from the use of statins to the FDA MedWatch program, using the information in the "Contact FDA" box at the bottom of the page.
  

Additional Information for Healthcare Professionals

• Healthcare professionals should perform liver enzyme tests before initiating statin therapy in patients and as clinically indicated thereafter. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, therapy should be interrupted. If an alternate etiology is not found, the statin should not be restarted.
• There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These reported symptoms are generally not serious and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
• Increases in glycosylated hemoglobin (HbA1c) and fasting serum glucose levels have been reported with statin use.
• Healthcare professionals should follow the recommendations in the lovastatin label regarding drugs that may increase the risk of myopathy/rhabdomyolysis when used with lovastatin (see Lovastatin Dose Limitations below).
• Healthcare professionals should report adverse events involving statins to the FDA MedWatch program using the information in the "Contact FDA" box at the bottom of this page.
  

Data Summary

Removal of routine monitoring of liver enzymes from drug labels

FDA reviewed current monitoring guidelines, including the National Lipid Association’s Liver Expert Panel and Statin Safety Task Force recommendations.^{1, 2} The Liver Expert Panel stated that the available scientific evidence does not support the routine monitoring of liver biochemistries in asymptomatic patients receiving statins. The Panel made this recommendation because (1) irreversible liver damage resulting from statins is exceptionally rare and is likely idiosyncratic in nature, and (2) no data exist to show that routine periodic monitoring of liver biochemistries is effective in identifying the very rare individual who may develop significant liver injury from ongoing statin therapy. The Panel believed that routine periodic monitoring will instead identify patients with isolated increased aminotransferase levels, which could motivate physicians to alter or discontinue statin therapy, thereby placing patients at increased risk for cardiovascular events.¹ The National Lipid Association’s Statin Task Force also stated that routine monitoring of liver function tests is not supported by the available evidence.²

FDA reviewed post-marketing data to evaluate the risk of clinically serious hepatotoxicity associated with statins. FDA had conducted several post-marketing reviews of statins and hepatotoxicity between years 2000 and 2009 by searching the Agency’s Adverse Event Reporting System (AERS) database. Those reviews consistently noted that reporting of statin-associated serious liver injury to the AERS database was extremely low (reporting rate of ≤2 per one million patient-years). FDA’s updated review focused on cases of severe liver injury, defined as a 4 (severe liver injury) or a 5 (death or liver transplant) using the Drug Induced Liver Injury Network (DILIN) liver injury severity scale, which were reported to AERS from marketing of each statin through 2009. Cases meeting those criteria were further assessed for causality. Seventy-five cases (27 cases with a severity score of 4, and 48 cases with a severity score of 5 (37 deaths and 11 liver transplants) were assessed for causality. Thirty of the 75 cases (14 deaths, 7 liver transplantations, and 9 severe liver injury) were assessed as possibly or probably associated with statin therapy. No cases were assessed as highly likely or definitely associated with statin therapy. FDA concluded that, despite a rising use of statins as a class since the late 1990s, there has not been a detectable increase in the annual rates of fatal or severe liver injury cases possibly or probably causally associated with statin use.

FDA also reviewed cases from the DILIN and Acute Liver Failure Study Group (ALFSG), organizations that have been submitting reports to FDA of drug-associated liver injury in their liver injury outcome studies. As of January 1, 2011, DILIN had submitted 25 reports of statin-associated liver injury to FDA, 12 of which gave hospitalization as an outcome. A 2010 article from ALFSG included 133 prospectively identified cases of idiopathic drug-induced liver injury resulting in acute liver failure.³ Of these 133 patients, 15 were taking statins, and in six of these 15 individuals a statin was identified as the only potential drug to cause drug-induced liver injury.

Based on all available data, FDA has determined that all currently marketed statins appear to be associated with a very low risk of serious liver injury and that routine periodic monitoring of serum alanine aminotransferase (ALT) does not appear to detect or prevent serious liver injury in association with statins.

Cognitive adverse events

FDA reviewed the AERS database, the published medical literature (case reports and observational studies),^4-13 and randomized clinical trials to evaluate the effect of statins on cognition.^14-17

The post-marketing adverse event reports generally described individuals over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon discontinuation of statin therapy. Time to onset of the event was highly variable, ranging from one day to years after statin exposure. The cases did not appear to be associated with fixed or progressive dementia, such as Alzheimer’s disease. The review did not reveal an association between the adverse event and the specific statin, the age of the individual, the statin dose, or concomitant medication use.

Data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline.

Increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose

FDA’s review of the results from the Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) reported a 27% increase in investigator-reported diabetes mellitus in rosuvastatin-treated patients compared to placebo-treated patients. High-dose atorvastatin had also been associated with worsening glycemic control in the Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis In Myocardial Infarction 22 (PROVE-IT TIMI 22) substudy.¹⁸

FDA also reviewed the published medical literature.^19-26 A meta-analysis by Sattar et al.,19 which included 13 statin trials with 91,140 participants, reported that statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17), with little heterogeneity (I2=11%) between trials. A meta-analysis by Rajpathak et al.,²⁰ which included 6 statin trials with 57,593 participants, also reported a small increase in diabetes risk (relative risk [RR] 1.13; 95% CI 1.03-1.23), with no evidence of heterogeneity across trials. A recent study by Culver et al.,²⁶ using data from the Women’s Health Initiative, reported that statin use conveys an increased risk of new-onset diabetes in postmenopausal women, and noted that the effect appears to be a medication class effect, unrelated to potency or to individual statin.

Based on clinical trial meta-analyses and epidemiological data from the published literature, information concerning an effect of statins on incident diabetes and increases in HbA1c and/or fasting plasma glucose was added to statin labels.

Lovastatin drug-drug interactions

Information regarding drug-drug interactions and contraindications and dose limitations has been added to the lovastatin label. Subsequent to the June 2011 label revisions to the simvastatin-containing products, which were based largely on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) trial,²⁷ a review of drug-drug interactions with lovastatin was conducted because the physicochemical and pharmacokinetic properties of lovastatin are comparable to those of simvastatin.

Lovastatin is a sensitive in vivo cytochrome P450 3A4 (CYP3A4) substrate. Strong CYP3A4 inhibitors are predicted to significantly increase lovastatin exposure. A literature review indicates that itraconazole, a strong CYP3A4 inhibitor, increases lovastatin exposure up to 20-fold and the drug interaction appears to result in rhabdomyolysis.²⁸ The effect of itraconazole on lovastatin exposure can therefore be extrapolated to other strong CYP3A4 inhibitors, including ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, human immunodeficiency virus (HIV) protease inhibitors, boceprevir, telaprevir, and nefazodone.

Lovastatin Dose Limitations

Previous lovastatin label	New lovastatin label
Avoid lovastatin with: Itraconazole Ketoconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone	Contraindicated with lovastatin: Itraconazole Ketoconazole Posaconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Boceprevir Telaprevir Nefazodone
Do not exceed 20 mg lovastatin daily with: Gemfibrozil Other fibrates Lipid-lowering doses (≥1 g/day) of niacin Cyclosporine Danazol	Avoid with lovastatin: Cyclosporine Gemfibrozil
	Do not exceed 20 mg lovastatin daily with: Danazol Diltiazem Verapamil
Do not exceed 40 mg lovastatin daily with: Amiodarone Verapamil	Do not exceed 40 mg lovastatin daily with: Amiodarone
Avoid large quantities of grapefruit juice (>1 quart daily)	Avoid large quantities of grapefruit juice (>1 quart daily)

References

1. Cohen DE, Anania FA, Chalasani N; for the National Lipid Association Statin Safety Task Force Liver Expert Panel. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97(8A):77C-81C.
2. McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8A):89C-94C.
3. Reuben A, Koch DG, Lee WM; for the Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology. 2010;52(6):2065-2076.
4. Orsi A, Sherman O, Woldeselassie Z. Simvastatin-associated memory loss. Pharmacotherapy. 2001;21:767-9.
5. Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23:871-80.
6. Evans MA, Golomb BA. Statin-associated adverse cognitive effects: survey results from 171 patients. Pharmacotherapy. 2009;29:800-811.
7. Parker BA, Polk DM, Rabdiya V, et al. Changes in memory function and neuronal activation associated with atorvastatin therapy. Pharmacotherapy. 2010;30(6):236e-240e.
8. Zamrini E, McGwin G, Roseman JM. Association between statin use and Alzheimer's disease. Neuroepidemiology. 2004;23:94-98.
9. Zandi PP, Sparks DL, Khachaturian AS, et al. Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry. 2005;62:217-224.
10. Zhou B, Teramukai S, Fukushima M. Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement Geriatr Cogn Disord. 2007;23:194-201.
11. Beydoun MA, Beason-Held LL, Kitner-Triolo MH, et al. Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment. J Epidemiol Community Health. 2011;65:949-957.
12. Bettermann K, Arnold AM, Williamson J, et al. Statins, risk of dementia, and cognitive function: secondary analysis of the Ginkgo Evaluation of Memory Study. J Stroke Cerebrovasc Dis. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2010.11.002³. Accessed January 31, 2012.
13. Benito-León J, Louis ED, Vega S, Bermejo-Pareja F. Statins and cognitive functioning in the elderly: a population-based study. J Alzheimers Dis. 2010;21:95-102.
14. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med. 2000;108:538-546.
15. Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004;117:823-829.
16. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85-90.
17. Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74:956-964.
18. Sabatine MS, Wiviott SD, Morrow DA, McCabe CH, Cannon CP. High-dose atorvastatin associated with worse glycemic control: a PROVE-IT TIMI 22 substudy. Circulation. 2004;110(Suppl I):S834.
19. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-742.
20. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32(10):1924-1929.
21. Sukhija R, Prayaga S, Marashdeh M, et al. Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med. 2009;57:495-499.
22. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209-1216.
23. Thongtang N, Ai M, Otokozawa S, et al. Effects of maximal atorvastatin and rosuvastatin treatment on markers of glucose homeostasis and inflammation. Am J Cardiol. 2011;107:387-392.
24. Kostapanos MS, Liamis GL, Milionis HJ, Elisaf MS. Do statins beneficially or adversely affect glucose homeostasis? Curr Vasc Pharmacol. 2010;8:612-631.
25. Mills EJ, Wu P, Chong G, et al. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials. QJM. 2011;104:109-124.
26. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med. 2012;172(2):144-152.
27. Armitage J, Bowman L, Wallendszus K; for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. , et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376:1658-1669.
28. Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med. 1995;333:664-555.

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Read the complete article here.

Alzheimer's: statin cure claims unfounded

Wed, 04 Apr 2012 15:33:00 EST

Cholesterol-lowering statin drugs “could stave off the symptoms of Alzheimer’s”, according to The Daily Telegraph. The front page of the Daily Express even boldly reported: “Statins halt Alzheimer’s.”

These attention-grabbing claims could easily lead readers to assume there has been a major breakthrough in the fight to cure Alzheimer’s disease. However, they are based on a small laboratory study which used mice that were bred to display signs of Alzheimer’s.

The early-stage research showed that the cholesterol-lowering drug simvastatin could improve learning and memory in mice genetically engineered to produce excess levels of amyloid protein in the brain, a characteristic feature of Alzheimer’s disease in humans. However, these improvements were only seen in younger mice, not older ones. The researchers took this to mean that statins would only be effective for blocking early-stage disease. The research also demonstrated that simvastatin caused some improvement in blood vessel function, which some researchers believe to be involved in developing the condition.

Even though these seem like positive results in mice, research has already looked directly at whether statins can stop Alzheimer’s and other forms of dementia in humans. For example, two recent high-quality reviews of research into statins and dementia suggest that there is no evidence that statins provide any specific benefit to humans with Alzheimer’s. While the new research suggests that the timing of statin use may allow it to have an effect, the evidence is far from conclusive and this would need to be explored further in a laboratory. Given the limitations of this research and the uncertainty over its results, the headline “Statins halt Alzheimer’s” is wildly misleading.

Dr Simon Ridley, head of research at Alzheimer’s Research UK, has put the study into context in a statement for Behind the Headlines. He said: “People should view the results with caution until further research has teased out how simvastatin might be working in these mice, and more importantly, until there is any significant new clinical trial data in humans.”

Where did the story come from?

The study was carried out by researchers from McGill University, Canada, and was funded by the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Canada. The study was published in the peer-reviewed Journal of Neuroscience.

Newspaper headlines about this research were generally misleading and suggested that it directly applies to humans. Most media reports took a few paragraphs, and in some cases half the article, to inform readers of the key fact that this research was carried out in mice and not humans. While the Daily Express’ headline suggests that statins have been proven to “halt Alzheimer’s”, this is not justified by the newly published research. In fact, the current body of high-quality research on this topic suggests the opposite is true.

What kind of research was this?

This laboratory study assessed the effect of simvastatin on different signs and symptoms of a mouse model of Alzheimer’s disease. Simvastatin is a widely used statin drug, which can control levels of cholesterol in the body. Around the world, many millions of middle-aged and elderly people take statins. To date, analysis of these populations has not detected any protective effect of the drug against dementia, including Alzheimer’s.

Laboratory studies in mice represent the early stages of medical research. During these mice-based studies, researchers are able to manipulate mice into displaying key characteristics of human disease, which they can then study in detail to better understand the condition in humans. For example, mice may be genetically modify to have biological characteristics similar to a human disease. However, there are key differences between mice and men, and early, experimental results from studies in mice may not always translate into similar findings in humans.

Alzheimer’s disease is characterised by the presence of deposits of the protein beta-amyloid in brain cells. These deposits are also known as amyloid plaques. These can interfere with the normal functioning of brain cells, causing the symptoms of memory loss and other deterioration in cognitive function commonly associated with Alzheimer’s disease. The authors of this study also said that Alzheimer’s is associated with problems in the blood vessels and blood circulation in the brain, and that previous research suggests this compromised blood flow could be related to the progression of Alzheimer’s.

Because statins can help keep blood vessels free of fatty build-up, some people have speculated that they could have a role in preventing Alzheimer’s disease. Previous reviews have not found an apparent link between statins and Alzheimer’s. However, the authors of this new research say recent evidence suggests that the cholesterol-lowering drugs may have beneficial effects on the development and progression of Alzheimer’s disease.

What did the research involve?

This study involved mice that were bred to produce excessive amounts of beta-amyloid protein in their brains, thereby mimicking the key biological characteristic of Alzheimer’s in humans. The research looked at the effect of the statin drug simvastatin on the levels of amyloid in the brain, as well as its effects on blood flow and blood vessel function in the brain.

The study used three main types of mice:

• mice bred to have Alzheimer’s-like disease who received simvastatin (treatment group)
• mice bred to have Alzheimer’s-like disease who didn’t receive simvastatin (control group)
• mice that were not bred to have Alzheimer’s-like disease or receive simvastatin (natural group)

Simvastatin was given to the treatment group mice in their drinking water, while controls were given the same amount of water without the statin. Simvastatin was administered at 20mg per kilo of body weight per day for 3 days. This was increased to 30mg/kg/day for 4 days, and then to 40mg/kg/day for the rest of the treatment.

The treatment group was further divided into two age groups: adult and aged. Adult mice were six months old and had been treated with statins from three months of age for a period of three months. Aged mice were twelve months old and had been treated from six months of age for six months. Total cholesterol levels were measured to assess the effect of the statin.

Spatial memory and learning were assessed with a commonly used water maze test. This involves placing a mouse into a small pool of water containing an escape platform hidden beneath the water’s surface. Visual cues indicate its location, and researchers record how quickly the mouse learns the location of the platform on repeated attempts. The visual cues and platform location can be changed to further assess learning and memory.

Three days after they had completed the maze task, mice were anaesthetised and the blood flow in their brains was measured using a standard technique. This involved using lasers to gauge the amount of fluid moving through their blood vessels. In a subset of mice, a small sample of artery blood vessel tissue was taken from their brain and subjected to laboratory experiments. These were designed to assess its ability to contract and relax as a normal functioning blood vessel should.

The researchers then used appropriate statistical analysis techniques to examine their results.

What were the basic results?

The key finding of this study was that simvastatin fully restored short- and long-term memory in adult mice, but not in aged mice. The researchers found that these beneficial effects occurred without a decrease in the amount of amyloid plaque found in the brains of the mice.

In addition, simvastatin restored key aspects of the functionality of the arteries in the brains of mice with Alzheimer’s disease. This functionality was impaired in mice that did not receive the statin.

How did the researchers interpret the results?

The researchers concluded that simvastatin, and possibly other brain-penetrating statins, show “high therapeutic promise” in early Alzheimer’s disease and in patients with vascular disease who are at risk of developing Alzheimer’s disease.

Conclusion

News reports of this research have ranged from optimistic to misleading. The study’s early mouse-based results need to be viewed in context, particularly as no benefit of statin use on Alzheimer’s has been found when directly examined in humans.

This study shows that the cholesterol-lowering drug simvastatin could improve blood vessel function and learning and memory in mice with features of Alzheimer’s-like disease, but only when given “early in the disease process” (when the mice were at a younger age). However, improved performance in a water maze may not necessarily demonstrate reversal of Alzheimer’s, particularly as the researchers found no decrease in the amount of amyloid plaque found in the brains of the mice. This means that even in mice, the statin had no effect on amyloid, a key characteristic in the human form of the disease.

Furthermore, a recent systematic review of the literature on statins and dementia (including Alzheimer’s disease, which is one type of dementia with strict diagnostic criteria) concluded that the use of statins to prevent vascular disease did not appear to prevent Alzheimer’s. It concluded that “there is good evidence [from randomised controlled trials] that statins given in late life to individuals at risk of vascular disease have no effect in preventing Alzheimer’s or dementia.” This review sought to identify all high-quality literature published on the topic, and it is unlikely that these conclusions would change on the basis of the new, small animal study.

Similarly, a systematic review also looked at whether statins were effective at treating dementia, using high-quality studies published before March 2009. It included a study that assessed the effect of simvastatin on Alzheimer’s disease. It too concluded that there was insufficient evidence to recommend statins for the treatment of dementia, including Alzheimer’s.

This research is bound to be of great interest to people with Alzheimer’s disease and their loved ones, particularly given the impression they may have gained from reading newspaper accounts of it. Dr Simon Ridley, head of research at Alzheimer’s Research UK, the UK’s leading dementia research charity, has helped put the research into context in a statement issued to Behind the Headlines. He said:

“These kinds of studies, in which some characteristics of Alzheimer’s in mice are prevented or reversed, are often interesting and can help to guide both understanding of the disease as well as future studies in people. While some studies in humans have suggested that statin users may have a lower risk of Alzheimer’s, this has not been consistent.

“However, as with many trials for chronic diseases, there is always the issue of whether there is a critical time to give treatments that offers the best chance of success.

“Although simvastatin is a cholesterol-lowering drug, this study in mice did not explain exactly how simvastatin was having its beneficial effect. Interestingly, there did not seem to be a reduction in cholesterol in the mice treated with simvastatin, suggesting that the drug may be acting through a mechanism independent of its ability to lower cholesterol. Therefore people should view the results with caution until further research has teased out how simvastatin might be working in these mice, and more importantly, until there is any significant new clinical trial data in humans.”

Consequently, while the research may offer scientists some new clues on the development of Alzheimer’s disease, front-page headlines that “Statins halt Alzheimer’s” are not supported by this small animal study or by the weight of existing research on the topic.

Analysis by Bazian

Links To The Headlines

Statins could stave off symptoms of Alzheimer's, study finds. The Daily Telegraph, April 4 2012

Widely-prescribed statins may help to fight Alzheimer's if they're given in early stages. Daily Mail, April 4 2012

Statins halt Alzheimer's. The Daily Express, April 4 2012
 

Links To Science

Tong XK, Lecrux C and Hamel E. Age-Dependent Rescue by Simvastatin of Alzheimer's Disease Cerebrovascular and Memory Deficits. The Journal of Neuroscience, 4 April 2012, 32(14): 4705-4715
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The Link between Nerve Damage and Statin Drugs

by Dr. Mercola
Spending on cholesterol-lowering drugs like statins increased by $160 million in 2010, for a total spending of nearly $19 billion in the U.S., the IMS Institute for Healthcare Informatics reported in their Use of Medicines in the United States: Review of 2010.
In all, more than 255 million prescriptions were dispensed for these drugs in 2010, making them the most commonly prescribed type of medication in the United States.
Unfortunately, this excessive use is an artifact of a medical system that regards prescribing pills to lower cholesterol as a valid way to protect one’s heart health — even though the low “target” cholesterol levels have not been proven to be healthy … and cholesterol is actually NOT the underlying culprit in heart disease.
Worse still, these drugs, which are clearly not necessary for the vast majority of people who take them, are proven to cause serious and significant side effects, including, as new research shows, definite nerve damage.

Are You Taking Drugs You Don’t Need … and Getting Nerve Damage as a Result?

It must be understood that any time you take a drug there is a risk of side effects.
Oftentimes, these risks are not fully understood, especially when multiple drugs enter the equation, and appear only after a drug has already been taken by millions of people.
Even once a drug has been FDA-approved, you are depending on a limited number of clinical trials to dictate a drug’s safety … but it’s impossible to predict how a drug will react when introduced into your system, in a real-world setting.
Not to mention, the accuracy of medical research is dubious at best.
In many ways, any time you take a drug YOU are the guinea pig, and unforeseen side effects are the rule, rather than the exception. In terms of statin drugs, side effects are already clearly apparent; at GreenMedInfo.com you can see 304 conditions that may be associated with the use of these drugs, and this is likely only the tip of the iceberg. Among one of the more well-known risks is harm to your muscles and peripheral nervous system with long-term use. Indeed, new research on 42 patients confirmed that:
” … long-term treatment with statins caused a clinically silent but still definite damage to peripheral nerves when the treatment lasts longer than 2 years.”

If You Take Statins for Two Years or More, Nerve Damage Appears to be the Rule

What does it mean when you sustain damage to peripheral nerves? As reported by the National Institute of Neurological Disorders and Stroke (NINDS):
“Symptoms are related to the type of affected nerve and may be seen over a period of days, weeks, or years. Muscle weakness is the most common symptom of motor nerve damage. Other symptoms may include painful cramps and fasciculations (uncontrolled muscle twitching visible under the skin), muscle loss, bone degeneration, and changes in the skin, hair, and nails.”
At GreenMedInfo.com you can see 88 studies on statin-induced neurotoxicity (nerve damage), with12 studies further statin drugs directly to neuropathy, including chronic peripheral neuropathy. As explained by NINDS:
“Peripheral neuropathy describes damage to the peripheral nervous system, the vast communications network that transmits information from the brain and spinal cord (the central nervous system) to every other part of the body. Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Like static on a telephone line, peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body.
Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged.
Some people may experience temporary numbness, tingling, and pricking sensations (paresthesia), sensitivity to touch, or muscle weakness. Others may suffer more extreme symptoms, including burning pain (especially at night), muscle wasting, paralysis, or organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, sweat normally, or experience normal sexual function. In the most extreme cases, breathing may become difficult or organ failure may occur.
Some forms of neuropathy involve damage to only one nerve and are called mononeuropathies. More often though, multiple nerves affecting all limbs are affected-called polyneuropathy.”
One of the more disturbing implications of this finding is that since statins damage the peripheral nerves, it is also highly likely that they damage the central nervous system (which includes the brain), as well. One study published in the journal Pharmacology in 2009, found statin-induced cognitive impairment to be a common occurrence, with 90% reporting improvement after drug discontinuation. There are, in fact, at least 12 studies linking memory problems with statin drug use in the biomedical literature, indicating just how widespread and serious a side effect statin-induced neurological damage really is.

Lower Your Cholesterol and Increase Your Diabetes Risk by Nearly 50%

As mentioned, neurological damage is only one potential risk of statins. They are also being increasingly associated with increased risk of developing diabetes.
Most recently, a study published in the Archives of Internal Medicine revealed statins increase the risk of diabetes for postmenopausal women by 48 percent! Statins appear to provoke diabetes through a few different mechanisms, the primary one being by increasing your insulin levels, which can be extremely harmful to your health. Chronically elevated insulin levels cause inflammation in your body, which is the hallmark of most chronic disease. In fact, elevated insulin levels lead to heart disease, which, ironically, prevention of is the primary reason for taking a statin drug in the first place!
As written on GreenMedInfo:
“The profound irony here is that most of the morbidity and mortality associated with diabetes is due to cardiovascular complications. High blood sugar and its oxidation (glycation) contribute to damage to the blood vessels, particularly the arteries, resulting in endothelial dysfunction and associated neuropathies due to lack of blood flow to the nerves. Statin drugs, which are purported to reduce cardiovascular disease risk through lipid suppression, insofar as they contribute to insulin resistance, elevated blood sugar, and full-blown diabetes, are not only diabetogenic but cardiotoxic, as well.”
A separate meta-analysis has also confirmed that statin drugs are indeed associated with increased risk of developing diabetes. The researchers evaluated five different clinical trials that together examined more than 32,000 people. They found that the higher the dosage of statin drugs being taken, the greater the diabetes risk. The “number needed to harm” for intensive-dose statin therapy was 498 for new-onset diabetes — that’s the number of people who need to take the drug in order for one person to develop diabetes.
In even simpler terms, one out of every 498 people who are on a high-dose statin regimen will develop diabetes. (The lower the “number needed to harm,” the greater the risk factor is. As a side note, the “number needed to treat” per year for intensive-dose statins was 155 for cardiovascular events. This means that 155 people have to take the drug in order to prevent one person from having a cardiovascular event.)
The following scientific reviews also reached the conclusion that statin use is associated with increased incidence of new-onset diabetes:

• A 2010 meta-analysis of 13 statin trials, consisting of 91,140 participants, found that statin therapy was associated with a 9 percent increased risk for incident diabetes. Here, the number needed to harm was 255 over four years, meaning for every 255 people on the drug, one developed diabetes as a result of the drug in that period of time.
• In a 2009 study, statin use was associated with a rise of fasting plasma glucose in patients with and without diabetes, independently of other factors such as age, and use of aspirin or angiotensin-converting enzyme inhibitors. The study included data from more than 345,400 patients over a period of two years. On average, statins increased fasting plasma glucose in non-diabetic statin users by 7 mg/dL, and in diabetics, statins increased glucose levels by 39 mg/dL.

Side Effects Often Don’t Show Up Immediately …

Oftentimes statins do not have any immediate side effects, and they are quite effective at lowering cholesterol levels by 50 points or more. This makes it appear as though they’re benefiting your health, and health problems that develop later on are frequently misinterpreted as brand new, separate health problems.
Again, the vast majority of people do not need statin drugs, and if you are one of them, taking them is only going to expose you to serious, unnecessary risks!
If your physician is urging you to check your total cholesterol, please be aware that this test will tell you virtually nothing about your risk of heart disease, unless it is 330 or higher. HDL percentage is a far more potent indicator for heart disease risk. Here are the two ratios you should pay attention to:

1. HDL/Total Cholesterol Ratio: Should ideally be above 24 percent. If below 10 percent, you have a significantly elevated risk for heart disease.
2. Triglyceride/HDL Ratio: Should be below 2.

To understand why most people don’t need a statin drug, you first need to realize that cholesterol is NOT the cause of heart disease. Your body NEEDS cholesterol — it is important in the production of cell membranes, hormones, vitamin D and bile acids that help you to digest fat. Cholesterol also helps your brain form memories and is vital to your neurological function. For more information about cholesterol, and why conventional advice to reduce your cholesterol to ridiculously low levels is foolhardy, please listen to this interview with Dr. Stephanie Seneff.

Urgent Information: If You Take Statins You Need CoQ10

It’s extremely important to understand that taking a statin drug without also taking CoQ10 puts your health in serious jeopardy. Unfortunately, this describes the majority of people who take them in the United States.
CoQ10 is a cofactor (co-enzyme) that is essential for the creation of ATP molecules, primarily in your mitochondria, which you need for cellular energy production. Organs such as your heart have higher energy requirements, and therefore require more CoQ10 to function properly (cardiac muscle cells have up to 200 times more mitochondria, and hence 200 times higher CoQ10 requirements, than skeletal muscle). Statins deplete your body of CoQ10, which can have devastating results.
As your body gets more and more depleted of CoQ10, you may suffer from fatigue, muscle weakness and soreness, and eventually heart failure. Interestingly, heart failure, not heart attacks, is now the leading cause of death due to cardiovascular diseases. Coenzyme Q10 is also very important in the process of neutralizing free radicals. So when your CoQ10 is depleted, you enter a vicious cycle of increased free radicals, loss of cellular energy, and damaged mitochondrial DNA.
If you decide to take a CoQ10 supplement and are over the age of 40, it’s important to choose the “reduced” version, called ubiquinol. The reduced form is electron-rich and therefore can donate electrons to quench free radicals, i.e. function as an antioxidant, and is much more absorbable, as nutrients must donate electrons in order to pass through membrane of cells. In other words, ubiquinol is a FAR more effective form — I personally take 200 mg a day since it has such far-ranging benefits, including compelling studies suggesting improvement in lifespan.

How to Optimize (Not Necessarily Lower) Your Cholesterol Without Drugs

Seventy-five percent of your cholesterol is produced by your liver, which is influenced by your insulin levels. Therefore, if you optimize your insulin level, you will automatically optimize your cholesterol! By modifying your diet and lifestyle in the following ways, you can safely modify your cholesterol without risking your health by taking statin drugs:

• Reduce, with the plan of eliminating, grains and sugars in your diet, replacing them with mostly whole, fresh vegetable carbs. Also try to consume a good portion of your food raw.
• The average American consumes 50% of their diet as carbs. Most would benefit by lowering their carb intake to 25% and replacing those carbs with high quality fats.
• Make sure you are getting enough high quality, animal-based omega 3 fats, such as krill oil.
• Other heart-healthy foods include olive oil, palm and coconut oil, organic raw dairy products and eggs, avocados, raw nuts and seeds, and organic grass-fed meats, as described in my nutrition plan.
• Exercise daily.
• Avoid smoking or drinking alcohol excessively.
• Be sure to get plenty of good, restorative sleep.

The goal of the tips above is not to necessarily lower your cholesterol as low as it can go; the goal is to optimize your levels so they’re working in the proper balance with your body.
Read the Full Article Here: http://articles.mercola.com/sites/articles/archive/2012/01/25/nerve-damage-with-cholesterol-meds.aspx


http://healthimpactnews.com/2012/the-link-between-nerve-damage-and-statin-drugs/